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Enalaprilat, losartan and LU 135252 in coronary blood flow regulation

M Rigol1, M Heras, N Solanes

  • 1Institut de Malalties Cardiovasculars, IDIBAPS, Hospital Clínic, Barcelona, Spain. mrigol@clinic.ub.es

European Journal of Clinical Investigation
|April 26, 2003
PubMed

Insights

Elevated angiotensin II impairs coronary blood flow during tachycardia. ACE inhibition, losartan, and endothelin-A receptor blockade restored flow, with ACE inhibition

Area of Science:

  • Cardiovascular Physiology
  • Pharmacology

Background:

  • High angiotensin II levels are implicated in cardiovascular diseases like hypertension.
  • The precise impact of elevated angiotensin II on coronary circulation, especially during increased heart rate, requires further elucidation.

Purpose of the Study:

  • To investigate how elevated coronary angiotensin II affects coronary blood flow regulation during tachycardia.
  • To evaluate the therapeutic potential of ACE inhibition, angiotensin II receptor blockade, and endothelin-A receptor antagonism in this context.

Main Methods:

  • Pigs underwent catheterization of the left anterior coronary artery for drug infusion.
  • Experimental groups received infusions of angiotensin II alone or in combination with enalaprilat, HOE 140 (bradykinin B2 antagonist), losartan, or LU 135252 (endothelin-A receptor antagonist).
  • Coronary blood flow was measured during atrial pacing before and after infusions.

Main Results:

  • Angiotensin II infusion significantly reduced the coronary blood flow increase during pacing.
  • Enalaprilat, losartan, and LU 135252 administration restored the hyperemic response to pacing.
  • The protective effect of enalaprilat was diminished by the bradykinin B2 antagonist HOE 140.

Conclusions:

  • Moderately increased coronary angiotensin II levels impair coronary blood flow regulation during tachycardia.
  • ACE inhibition, angiotensin II receptor blockade, and endothelin-A receptor blockade effectively restore coronary hyperemic capacity.
  • The beneficial effects of ACE inhibition in this model are mediated by bradykinin.
Abstract

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